Early work carried out by such investigators as R. Kiessling, R. B. Herberman and R. K. Oldham confirmed the existence of natural cytotoxic reactivity by lymphoid cells taken from human donors. This naturally occurring cell mediated cytotoxicity in vitro has subsequently been investigated and confirmed in the mouse and in humans by the foregoing investigators and others.
The effector cells mediating natural cell mediated cytotoxicity are collectively known as natural killer cells. Natural killer cells were initially defined in a negative way, i.e., as cells lacking some characteristic features of cytotoxic T lymphocytes and other typical T cells, B cells, monocytes or granulocytes. Additional identification work has demonstrated a number of positive features such as, for example, that the natural killer activity is not diffusely distributed among a variety of different types of lymphoid cells but rather is restricted to a discrete subpopulation of cells comprising only 5 to 10 percent of the peripheral blood mononuclear cells. Almost all such cells have also been shown to express receptors for the the Fc portion IgG. Human natural killer cells have also been found to have several other characteristic cell surface markers, including markers that have been closely associated with typical T cells. While these characterizations serve to construct a picture of the natural killer cells a definitive characterization is not presently available.
In addition, the spontaneous appearance of cell mediated cytotoxicity remains undefined. A number of factors have been suggested as the activating mechanism, for example environmental factors such as bacteria parasites, viruses or similar agents have been implicated as causitive agents for the inducement of natural killer cell activity. Genetic factors have also been alleged to play a role in the appearance of natural killer cell activity
Another apparently important activator for natural killer cell activity is interferon. Normal mice treated repeatedly with antibodies to interferon have shown a substantial but not complete reduction in their spontaneous natural killer cell activity indicating endogenous interferon may contribute to the spontaneous development of natural killer cell activity.
A representative overview of cell mediated cytotoxicity is given by Herberman, R. B. and R. K. Oldham, Journal of Biological Response Modifiers, 2:111-120 (1983) and Stutman, O. et al, Federation Proceedings, 40 (12):2699 (1981).
This invention relates to nonapeptides and dodecapeptides which are taken in whole or in part from the N-terminus of a polypeptide which is a transcription of a DNA fragment determined to be the producer of the protein portion of human interferon gamma, though the native material, human interferon gamma has not been fully sequenced and identified. It has been determined that the nonapeptide between positions 4 and 12 of the N-terminal portion of this protein augments natural killer cell activity.